Biodegradable and bioabsorbable implant material and method for adjusting shape thereof

ABSTRACT

This invention provides a biodegradable and bioabsorbable implant material having a high mechanical strength wherein its shape after deformation within ordinary temperature range can be fixed and maintained so that its shape can be easily adjusted at the site of operation, and it has substantially no anisotropy in view of strength so that it does not cause whitening, breakage and sharp decrease in strength when its bending deformation is repeated in any direction and it has toughness. Particularly, it provides an implant material which comprises a biodegradable and bioabsorbable crystalline polymer that has a crystallinity of 5% or more, can effect deformation such as bending or twisting within ordinary temperature range and has a shape-keeping ability to fix and maintain the shape after deformation as such, wherein molecular chains, domains of molecular chain assembly or crystals of the polymer are oriented along a large number of reference axes having different axial directions, or clusters having these reference axes having different orientation are assembled in a large number.

FIELD OF THE INVENTION

This invention relates to a convenient biodegradable and bioabsorbableimplant material which is a biomaterial having high mechanical strengthand less mechanical anisotropy, can easily be deformed by bending and/ortwisting within ordinary temperature range, has an ability to fix andkeep its shape after the deformation as such and can be adjusted into ashape adapted to the surface shape of the region to be applied in theliving body in using as such devices of plates, pins and wires.

BACKGROUND OF THE INVENTION

There are various types of implant materials to be implanted in theliving body; for example, devices such as plates, pins and wires made ofmetals or ceramics are frequently used in the case of osteosynthesis.

However, being extensively high in elastic modulus in comparison withnatural bones, these implant materials have a problem of reducingstrength of peripheral bones due to a stress reducing phenomenon afterhealing and are excessive shielding strength. Particularly, in the caseof implant materials made of metals, they have problems in that elutionof metal ions may exert bad influences upon the living body, sometimescausing a danger of generating carcinogenicity and that, when they areleft in the living body for a prolonged period of time after completionof their role such as osteosynthesis, they inhibit natural growth ofbones so that it is suitable to carry out re-operation to take out theimplant devices from the living body at an early stage after healingsuch as of bone fracture.

Accordingly, studies have been carried out on biodegradable andbioabsorbable implant materials, and devices for osteosynthesis whichare molded with a polyglycolic, a polylactic acid or a copolymer thereofhave been developed. Such materials for osteosynthesis, particularly thematerials for osteosynthesis made of a polylactic acid, arebiocompatible because of their good affinity for the alive body and havea favorable property in that they are gradually hydrolyzed in the livingbody by the contact with body fluids and finally absorbed by the livingbody, so that they are frequently used in recent years. In addition, itis not necessary to remove them by re-operation, which is different fromthe case of the implant devices made of metals.

However, a mini-plate material, etc. made of titanium for use in oraland maxillofacial surgery and brain surgery has an advantage in that itcan be used by freely deforming its shape during operation to exertsufficient fixing ability by closely adjusting it to the shape of boneto be treated. Accordingly, in many cases, the same characteristics,i.e., bend-deforming the devices to conform to the shape of the boneupon use, is also in demand for implant devices such as plates forosteosynthesis molded with polylactic acid. As a matter of course, amaterial prepared to have a flat type shape may be used as such in somecases. Such a plate can be used in the scene of operation bythermoforming it at a temperature of approximately from 60 to 80° C. toadjust it to the shape of the surface of bone to be treated. Although itis a practical method which uses conventional knowledge on thethermoorming of plastics, it requires complex handling.

In general, a molding of polylactic acid having a flat shape such asplate can be easily deformed by bending at ordinary temperature when thethickness is thin. However, when its bending deformation is carried outat an ordinary temperature which is lower than its glass transitionpoint (Tg), whitening occurs in the bending-deformed part portion due tochange of the morphology and its strength is reduced, thus causing aproblem in that it cannot be used as a plate for osteosynthesis. Thus,in reality, its bending deformation has to be made by heating andsoftening it as described in the foregoing.

In the polylactic acid implant materials so far developed, uniaxialdrawing is carried out by various methods for the purpose of increasingstrength, and the polymer molecules and crystals are oriented along thedrawing direction by this treatment. At the same time, the polymerbecomes fibers when the draw ratio is increased. By the use of theirassembled form, a device for osteosynthesis having markedly increasedstrength of mechanical direction (MD) can be prepared. However, since animplant device in which the polymer molecules are uniaxially oriented inthis manner has considerably large anisotropy. Accordingly, the bentpart whitens and is easily broken when it is bending-deformed atordinary temperature by merely a small number of times but to adirection falling at right angle with the orientation direction. It alsocauses a problem in that it is easily broken when twisted in theorientation direction around the sequence of fibers. Accordingly, it isalso difficult to carry out torsional deformation.

In addition, there are other unsolved problems in that, since implantmaterials solely made of a polylactic acid have no ability to bond tobones, bones cannot be fixed securely because of a possibility to causeloosening after its application to bones. In addition, since they haveno bone conductivity, their replacement by bones after degradation andabsorption cannot be easily completed.

The present invention was accomplished by taking the aforementionedproblems into consideration. The object of the present invention is toprovide a biodegradable and bioabsorbable implant devices which havebasically large mechanical strength, can be deformed by bending ortwisting within ordinary temperature range and can fix and keep theresulting shape as such, has substantially no anisotropy of strength,can be subjected to repeated deformation of exceeding 20 times (canwithstand repeated deformation of more than several hundred times in thecase of a wire having a circular section) because of its ability of noteasily causing whitening and reduced strength by its deformation in anydirection partially due to the change of morphology, and also can give aproperty to bond to bones within a short period of time as well as abone conductivity.

SUMMARY OF THE INVENTION

In order to achieve the aforementioned object, the biodegradable andbioabsorbable implant material according to the first embodiment of thepresent invention is characterized in that it comprises a biodegradableand bioabsorbable crystalline polymer capable of effecting deformationsuch as bending or twisting within ordinary temperature range and havinga shape-keeping ability to fix and maintain the shape after deformationas such, wherein molecular chains, domains of molecular chain assemblyor crystals of the biodegradable and bioabsorbable polymer are orientedalong a large number of reference axes having different axialdirections, or clusters having these reference axes having differentorientation are assembled in a large number.

The term “orientation along a large number of reference axes havingdifferent axial directions” or “assembly of clusters having referenceaxes of different orientation” means a multi-axial orientation or anoriented form as the assembly of multi-axially oriented clusters, sothat its meaning is completely different from that of no orientationwhich means no oriented form (so-called randomly oriented form having noorientation treatment). Also, the term “ordinary temperature range”means a temperature range of from 0° C. or more to less than 50° C.

Also, the biodegradable and bioabsorbable implant material according tothe second embodiment of the present invention is the implant materialas set forth in the first embodiment, wherein it is obtained by forginga billet comprising a biodegradable and bioabsorbable crystallinepolymer at a low temperature between Tg and less than Tm (Tg: glasstransition temperature; Tm: melting temperature) and then forging it atthe temperature by changing its mechanical direction (MD) (which may becarried out a plurality of times), and the biodegradable andbioabsorbable implant material according to third embodiment of thepresent invention uses a crystalline polylactic acid as thebiodegradable and bioabsorbable crystalline polymer. Also, thebiodegradable and bioabsorbable implant material according to the fourthembodiment of the present invention is an implant device forosteosynthesis use which is formed into a flat heteromorphic shape suchas a sheet, a plate, a plate having screw-inserting hole(s), a washer, abutton, a mesh or a ribbon, the biodegradable and bioabsorbable implantmaterial according to the fifth embodiment of the present invention isan implant device which is formed into a cylindrical shape such as awire, a cable prepared by making up thin wires into a bundle andtwisting the bundle, a rod or a pin, and the biodegradable andbioabsorbable implant material according to the sixth embodiment of thepresent invention is characterized in that it further contains abioceramics powder. In this connection, the “billet” of the secondembodiment of the present invention is not limited to a round bar andits shape is not limited, so that it may be a polygonal prism havingdifferent number of angles. The seventh embodiment of the presentinvention is a biodegradable and bioabsorbable implant material whereinthe state of orientation of molecular chains, domains of molecular chainassembly or crystals of the biodegradable and bioabsorbable polymerpartially changes by the deformation within ordinary temperature.

In addition, the shape-adjusting method of eight embodiment of thepresent invention is characterized in that the biodegradable andbioabsorbable implant material as set forth in any one of theaforementioned first to seventh embodiments of the present invention issubjected to bending deformation and/or torsional deformation withinordinary temperature range and then the shape after deformation is fixedand kept as such.

Other objects and advantages of the present invention will be madeapparent as the description progresses.

BRIEF DESCRIPTION OF THE DRAWINGS

Each of FIGS. 1A to 1F is an illustration showing plan view of abiodegradable and bioabsorbable implant device for osteosynthesis use,in which 1A is a straight type material, 1B is an L type, 1C is a Ttype, 1D is a Y type, 1E is a C type and 1F is a straight type having no“necking”, and 1G in the drawing is an illustration showing plan view ofa ribbon-shaped biodegradable and bioabsorbable implant material fororthopaedic surgery use. In the drawing, 1 is a screw insertion hole.

FIG. 2 is a sectional view of a forming mold for producing thebiodegradable and bioabsorbable implant material of the presentinvention.

FIG. 3A and FIG. 3B show the crystalline orientation state of themolding forged one time. FIG. 3A is a side view and FIG. 3B is a planview.

FIG. 4 is a drawing showing the mechanical directions (MD) of the forgedmolding.

FIG. 5 is an explanatory drawing showing a way of cutting out arectangular plate from a plate-shaped compression multi-axialorientation molding in Example 1.

FIGS. 6A and 6B are explanatory drawings showing the repeated bendingtest carried out in Example 1. In the drawings, 2 is an autograph crosshead and P is a plate.

FIG. 7 is a graph showing a relationship between the number of times ofbending deformation and the retaining ratio of bending strength,examined using a plate of Example 1 having a cut out direction of 0° anda plate of Comparative Example 1 having a cut out direction of 0°.

FIG. 8 is a graph showing a relationship between the number of times ofbending deformation and the retaining ratio of bending strength,examined using a plate of Example 1 having a cut out direction of 45°and a plate of Comparative Example 1 having a cut out direction of 45°.

FIG. 9 is a graph showing a relationship between the number of times ofbending deformation and the retaining ratio of bending strength,examined using a plate of Example 1 having a cut out direction of 90°and a plate of Comparative Example 1 having a cut out direction of 90°.

FIG. 10 is an explanatory drawing showing the repeated bending test of awire carried out in Example 3, in which 10A shows a fixed condition ofthe wire, 10B shows a condition bent downward at 15° and 10C shows acondition upward at 15°.

FIG. 11 is a graph showing a relationship between the number of times ofbending deformation and the retaining ratio of bending strength,examined using a wire of Example 3 and a kirschner wire.

FIGS. 12A and 12B are X ray photographs of the molding forged one time.FIG. 12A is an X ray photograph when the incident angle of the X ray wasparallel to the mechanical direction MD1. FIG. 12B is an X rayphotograph when the incident angle of the X ray was right to themechanical direction MD1.

FIGS. 13A and 13B are X ray photographs of the molding forged two timesaccording to the present invention. FIG. 13A is an X ray photograph whenthe incident angle of the X ray was parallel to the mechanical directionMD2. FIG. 13B is an X ray photograph when the incident angle of the Xray was right to the mechanical direction MD2.

FIG. 14 is a drawing explaining the morphological change of theorientation.

DETAILED DESCRIPTION OF THE INVENTION

A crystalline plastic having a glass transition point (Tg) of lower thanthe usual room temperature (from 25 to 30° C.) generally has amorphological phase structure comprising a crystal phase and a rubberphase at room temperature. Because of the presence of rubber layer, theshape after its bending within ordinary temperature range can hardly bekept and fixed and is restored by its elasticity. Polyethylene (Tg: −20°C.) and polypropylene (Tg: −10° C.) are its familiar examples, and whenthey are deformed within the ordinary temperature range defined by thepresent invention and then the external force is removed, they arerestored to the original shape or a shape close to the original shape bythe rubber elasticity.

On the contrary, a crystalline polylactic acid or the like as a typicalexample of the biodegradable and bioabsorbable polymer to be used in thepresent invention has a glass transition point (Tg) of higher than theordinary temperature range (60 to 65° C.), shows a phase structuremainly comprising a crystal phase and a glass phase within the ordinarytemperature range and contains substantially no rubber phase even whenthe crystallinity is at least 5% or more, so that its shape afterbending deformation within the ordinary temperature range can be keptand fixed as such. The aforementioned polymer such as polylactic acid isan assembled body in view of material morphology in which molecularchains, domains of molecular chain assembly or crystals of the polymerare oriented along a large number of reference axes having randomlydifferent axial directions (that is, expression of three-dimensionalorientation of a plurality of axial directions is found statistically)or clusters having reference axes having randomly different orientationare assembled in a large number, so that such a deformation propertycapable of keeping and fixing its shape after bending or twistingtreatment is expressed by the generation of mutual “shearing” betweensurfaces of these assembled masses. Accordingly, it is considered that,when deformation is effected in a certain direction, an assembled bodyhaving a crystal phase oriented along that direction is formed, so thatit acts as a back up of strength in the deformation direction and,therefore, durability of repeated deformation is generated even againstvarious deformation directions and twisting.

Among the aforementioned polylactic acids, a crystalline poly-L-lacticacid as L-isomer homopolymer and an crystalline poly-D-lactic acid as aD-isomer homopolymer are basically composed of a crystal phase and aglass phase, but a poly-D/L-lactic acid as a copolymer of D-isomer andL-isomer keeps back a crystal phase when the molar ratio of any one ofthe D-isomer and L-isomer exceeds 80% (88% according to a certainliterature) and, when the ratio is 80% or less, the crystal phase mostlydisappears and the polymer becomes basically glassy. In consequence,when a ploy-D/L-lactic acid is used, it is desirable to use a copolymerhaving a D-isomer/L-isomer molar ratio of approximately 80/20 or more orapproximately 20/80 or less and a remaining crystallinity ofapproximately 5% or more. The Tg value of such a poly-D/L-lactic acidhaving a crystallinity of 5% or more and the Tg values of theaforementioned poly-L-lactic acid poly-D-lactic acid are higher than 50°C. which is the upper limit of the “ordinary temperature range” of thepresent invention. That is, the present invention relates to a materialhaving a characteristics that it is freely deformed and fixed at atemperature which is equal to or less than its Tg value and also relatesto a deformation method thereof. The ordinary temperature rangeeffective for deformation and fixing is employed as a particularcharacteristic of the present invention. When a billet of such acrystalline polymer is forged at low temperature between Tg and lessthan Tm and again forged once or a plurality of times at the temperatureby changing its mechanical direction such as the case of the secondembodiment of the present invention, an implant device having lessanisotropy in view of strength and markedly higher strength than thatbefore the forging is obtained. It is considered that such an effect isobtained due to formation of the orientation of molecular chain assemblydomains and the orientation of crystals based on the intermolecular andintramolecular mutual actions generated by the aforementioned particulartemperature processing of the present invention. In addition, packingdensity of the material of a molding is considerably increased withouthaving directional property by the pressure added toward the directionof the central part of a billet at the time of its forging treatment.

In order to orient molecular chains, domains of molecular chain assemblyor crystals of an implant material forged in the aforementioned manneralong a large number of reference axes in which axial directions arearranged in many directions, the forging is effected at a temperature ofapproximately from 70 to 130° C. which is considerably higher than theordinary temperature but fairly lower than the usual thermoformingtemperature. Therefore, when the implant material is deformed within theordinary temperature range and embedded in the living body, the crystalphase which does not melt at ordinary temperature behaves as a back upstructure phase at the time of deformation (the temperature Tm at whichthe crystal phase melts is about 180° C. which is fairly high)Accordingly, the shape after deformation is maintained as such and doesnot remember to its original shape by the body temperature. In otherwords, restoration of the original shape through disappearance of theorientation requires a temperature rising at least to a level of theforging-treated temperature or more, but the forging temperature iswithin the range of from 70 to 130° C., which is fairly higher than thebody temperature as described in the above, so that it does not rememberto its original shape.

On the other hand, when bending deformation is carried out within theordinary temperature range with respect to a non-oriented material inwhich molecular chains, domains of molecular chain assembly or crystalsdo not have the aforementioned orientation modes or a material having anorientation only in a single direction (uniaxial direction), a large“shear” is easily formed in the deformed part and produces amorphological part a configuration which is different from theperipheral non-deformed parts, thus resulting in the formation ofmicroscopic faults, so that whitening occurs sometimes which easilyentails cutting failure of the material. However, in the case of amaterial in which molecular chains, domains of molecular chain assemblyor crystals are multi-axially oriented, or multi-axially orientedclusters are assembled, as in the case of the implant material of thepresent invention, it does not cause whitening when bending deformationis carried out in any direction over a large number of times incomparison with a non-oriented or single direction-oriented material sothat cutting failure of the material does not occur. In addition,reduction of strength (deterioration) at that time is very little andabout 80% or more of the initial bending strength is maintained afterrepeated bending deformation, as is evident from the test data whichwill be described later. Such a feature is far superior to that of atitanium plate which has ductility and toughness and can easily bedeformed at the site of surgical operation. In consequence, when theimplant material of the present invention is subjected to bendingdeformation and/or torsional deformation within ordinary temperaturerange and the shape after deformation is fixed and kept as such, as inthe case of the shape-adjusting method of the seventh embodiment of thepresent invention, decisive reduction of strength does not occur so thatthe implant device can be embedded in the living body by easilyadjusting its shape during the operation. Such an excellent mechanicalproperty cannot at all be obtained by the conventional biodegradable andbioabsorbable implant material without orientation or with uniaxialorientation. This is also an essential characteristic when aheteromorphic plate which will be shown later by drawings is used by itsdeformation.

The aforementioned biodegradable and bioabsorbable implant material isformed, for example, into an implant device for osteosynthesis use,having a flat heteromorphic shape such as a sheet, a plate, a platehaving screw-inserting hole(s), a washer, a button, a mesh or a ribbon,as in the case of fourth embodiment of the present invention, and usedfor the bone healing at the site of operation by adjusting its shape tothe irregular surface shape of bones through its bending deformation ortorsional deformation within the ordinary temperature range. Such animplant material for osteosynthesis use may be a material in which aflat plate is slightly bent or twisted in advance to a predeterminedshape. As in the case of the fifth embodiment of the present invention,it is also formed into a round or square cylindrical shape such as awire, a cable prepared by making up thin wires into a bundle andtwisting the bundle, a rod or a pin and used at the site of operation,for example, by twist-deforming it as a wire for bone healing orbend-deforming it in response to the bending degree of bones to behealed.

In that case, when a bioceramics powder is included as in the case ofthe implant material of the sixth embodiment of the present invention,the bioceramics powder exerts an action to deposit and form calciumphosphate existing in the living body on the surface layer of theimplant material, so that the implant device binds to the device bonewithin a relatively short period of time. In consequence, looseninghardly occurs and the fractured bones can be fixed securely. It alsoexpresses a property to conduct formation of new bone to a lost boneregion which is formed when the said implant device is embedded. It isfurther effective, because the implant material as a whole is absorbedin the living body and finally disappears at a relatively early stagereplaced by the biological bone.

Illustrative embodiment of the present invention is described in detailin the following with reference to the drawings.

Each of FIGS. 1A to 1F is an illustration showing plan view of abiodegradable and bioabsorbable implant device for osteosynthesis use,in which 1A is a straight type material, 1B is an L type, 1C is a Ttype, 1D is a Y type, 1E is a C type and 1F is a straight type having no“necking”,and 1G in the drawing is an illustration showing plan view ofa ribbon-shaped bone healing and fixing material for plastic surgeryuse.

Each type of the implant material is formed into a plate shape ofapproximately from 0.5 to 3.5 mm in thickness having a plurality ofscrew insertion hole 1, which can be deformed by its bending or twistingwithin ordinary temperature range (0° C. or more and less than 50° C.)and has a function to fix and keep its shape after deformation. When thethickness is thinner than 0.5 mm, its strength as a plate forosteosynthesis use may become insufficient. When the thickness is largerthan 2.0 mm, a prolonged period of time is required until its completedegradation and disappearance of tactile perception (3 years or more) sothat it can hardly be used in the field of oral surgery. When thethickness exceeds 3.5 mm, its weight becomes so heavy that it isnecessary to avoid its use even in the field of orthopaedic surgery inorder to prevent side effects at the time of its degradation andabsorption. Also, since a considerably large force is required for itsbending deformation or torsional deformation within the ordinarytemperature range, free deformation cannot be made easily.

In addition, though not shown in the drawings, it may have a round orsquare cylindrical shape such as a wire, a cable prepared by twistingthe wires, a rod or a pin. A cylindrical material having, for example, adiameter of from 0.5 to 4.0 mm and a length of from 10 to 30 cm is used,which can be bent, twisted or deformed for example for ligation and isapplicable to materials for osteosynthesis use (e.g., pins, wires andthe like). It also can be formed into a thin band shape such as asheet-like ribbon, and such a ribbon has a thickness of from 0.2 to 2.0mm and a length of from 10 to 30 cm and can be bent, twisted or deformedfor example for ligation.

Since these implant devices comprise a biodegradable and bioabsorbablecrystalline thermoplastic polymer having a glass transition point (Tg)of higher than room temperature, they have a phase structure basicallycomposed of a crystal phase and a glass phase and their crystallinity is5% or more. However, it is preferable that the upper limit of thecrystallinity does not exceed 70%, because a large number of fine piecesof crystals are formed simultaneously with the degradation of theimplant materials as their degradation progresses. Since the amount ofthe thus formed fine pieces of crystals far exceeds the phagocitosingcapacity of macrophages, there is a possibility of causing damage uponperipheral cells and thereby generating inflammation. Also, when thecrystallinity exceeds 70%, the polymer loses its toughness andflexibility and becomes brittle, so that molding of the material becomesdifficult. In consequence, it is desirable that the crystallinity is 70%or less, preferably from 30 to 50%. In addition, the material comprisesa multi-axially oriented form in which molecular chains, domains ofmolecular chain assembly or crystals of the biodegradable andbioabsorbable polymer are oriented along many reference axes havingrandom axial directions, or an assembled mass in which clusters havingreference axes of randomly different orientation are assembled in alarge number.

In consequence, these implant materials are practical because, asdescribed in the foregoing, they have substantially no mechanicalanisotropy, are not easily broken when bending-deformed in any directionwithin the ordinary temperature range which is different from the caseof a non-oriented or single direction-oriented implant material, showsvery little reduction of strength (deterioration) by repeated bendingand maintains about 80% or more of the initial bending strength afterrepeated bending deformation of exceeding 20 times, so that the strengthis hardly reduced after several times of deformation at ordinarytemperature during operation. Also, in the case of a wire havingcircular section, it is not broken after 800 times of repeated bendingat an upward/downward angle of 15° as will be shown later in Example 3.While a kirschner wire is broken by about 400 times of bending, thiswire has such a durability that its initial strength can be maintainedduring 800 times of bending.

The aforementioned implant materials can be produced by preparing abillet from a biodegradable and bioabsorbable crystalline polymer,forging the billet at a low temperature (glass transition temperature ormore and less than melting temperature, preferably from 70 to 130° C.,more preferably from 90 to 110° C.), further forging at a lowtemperature by changing its mechanical direction (MD) to make a plate-or rod-shaped multi-axially oriented body or an assembly of orientedclusters, and then cutting it into various flat plate shapes shown inFIGS. 1A to 1G while simultaneously carrying out a perforationprocessing. A wire can be produced by cutting the forged plate-shapedmolding into a prismatic shape and processing the prism by removing itscomers so that its section becomes circular.

The implant material of the present invention can be prepared, forexample, by the method described below. First, a crystallizablebiodegradable and bioabsorbable polymer is made into a billet 10 by theknown molding method (e.g., the extrusion molding and the injectionmolding) at a temperature that is higher than the melting point of thepolymer and lower than 220° C. As shown in FIG. 2, the resulting billet10 is pressed into a small space of the bottom-closed forming mold 20having a smaller thickness, diameter, etc. than that of the billet 10,while effecting plastic deformation at a low temperature between Tg andless than Tm, to prepare a forged molding block (plate, billet) 11.Then, the resulting forged molding block 11 is pressed into a smallspace of the bottom-closed forming mold having a smaller thickness,diameter, etc. than that of the forged molding block 11, while effectingplastic deformation at a low temperature between Tg and less than Tm, toprepare the molding 1 of the present invention.

The forming mold 20 shown in FIG. 2 is an example of the forming moldingfor preparing a plate-shaped forged molding block 11. The formingmolding 20 comprises (1) a mold which comprises a part forming a cavity21 having a rectangular longitudinal section and having a larger lateralsectional area, in which the billet 10 is filled, a bottomed partforming a cavity 22 having a rectangular longitudinal section and havinga smaller lateral sectional area (preferably, about ⅔ to ⅙ of thesectional area of the billet), and the tapered part 23 connecting thesetwo and having a trapezoid longitudinal section, wherein these threeparts aligned along the same central axis; and (2) a piston 24 which canbe inserted into the cavity 21.

The billet 10 filled in the cavity 21 is press-forced into the cavity 22by continuously or discontinuously applying a pressure, while effectingplastic deformation at a low temperature. The direction of thispress-forcing is the mechanical direction MD1. The polymer crystallizesby this forging molding. As shown in FIG. 3A, the crystals of thepolymer align in parallel in the directions of a large number ofreference axes N that slant toward the axial face M. In this regard, theaxial face M is the mechanical core during the molding, i.e., the areacontaining the continuous points (lines) at which the forces from theboth sides of the forming mold are concentrated.

The crystallized forged molding block 11 as it is or after cutting intoan appropriate size is then subjected to the second forging molding bychanging the mechanical direction MD (i.e., changing the direction ofpress-forcing). The forming mold used for the second forging molding maybe the similar shape with the above-described forming mold 20. That is,the forming molding comprises (1) a mold which comprises a part forminga cavity having a rectangular longitudinal section and having a largerlateral sectional area (having a smaller laterial sectional area thanthat of the forged molding block 11), in which the forged molding block11 is filled, a bottomed part forming a cavity having a rectangularlongitudinal section and having a smaller lateral sectional area(preferably, about ⅔ to ⅙ of the sectional area of the forged moldingblock 11), and the tapered part connecting these two and having atrapezoid longitudinal section, wherein these three parts aligned alongthe same central axis; and (2) a piston which can be inserted into thecavity. The forged molding block 11 is filled into the cavity of theforming molding in a certain direction so that the press-forcingdirection of the second forging molding (MD2) becomes different from thepress-forcing direction of the first forging molding (MD1). For example,as shown in FIG. 4, MD2 is selected to form an angle of 900 against MD1.Then, the forged molding block 11 is press-forced into the cavitycontinuously or discontinuously, while effecting plastic deformation atlow temperature. By this second forging molding, the crystals of thepolymer which have been oriented in parallel along many reference axesare subjected to the rearrangement in the mechanical direction, so thatthe many reference axes direct toward various directions randomly. As aresult, the crystals of the polymer are oriented along a large number ofreference axes having different axial directions, or clusters havingthese reference axes having different orientation are assembled in alarge number. The molecular chains and domains of the molecular chainsof the polymer are similarly oriented.

In the foregoing, the molding obtained by two times forging moldings wasexplained. It is possible to conduct further forging molding. The numberof total forging moldings is preferably from 2 to 5, more preferablyfrom 2 to 3, because the reference axes along which the crystals orienthardly becomes random and the device obtained can bear to the outerforces such as bending, twisting, etc. in these ranges. Between theforging molding steps, the directions of the press-forcing are changedso as to form an angle in the range of preferably from 10° to 170°, morepreferably from 45° to 1350, most preferably 90°.

It is desirable to carry out the forging at such a deformation ratio(sectional area of a billet/sectional area of its forged molding) thatfibrillation does not occur, preferably at a deformation ratio of from1.1 to 3.5.

Crystalline thermoplastic polymers having a crystallinity of 5% or more,which have a glass transition point (Tg) of higher than the upper limitof the ordinary temperature range (50° C.) and are hydrolyzed andabsorbed in the living body, are used as the biodegradable andbioabsorbable material polymers, among which polylactic acids having aninitial viscosity average molecular weight of from 100,000 to 700,000,preferably from 150,000 to 400,000, namely a poly-L-lactic acid, apoly-D-lactic acid and a poly-D/L-lactic acid (provided that it is acopolymer having a D/L molar ratio of approximately 80/20 or more orapproximately 20/80 or less and having a crystallinity of 5% or more)are desirable, and these polymers may be used alone or as a mixture oftwo or more. A polymer having a crystallinity of from 10 to 70%,preferably from 30 to 50%, is particularly desirable.

A biodegradable and bioabsorbable amorphous polymer having acrystallinity of less than 5%, such as a poly-D/L-lactic acid having aD/L molar ratio of 50/50 and a crystallinity of 0%, shows a certaindegree of improvement in strength when it is compressed by forging at alow temperature. However, because of its basically small strength, it isdifficult to obtain an implant material which has such a toughness thatit does not break by 20 or more times of repeated bending deformation,and such an implant material is apt to return to its original shape whencompared with a crystalline polymer, so that the object of the presentinvention cannot be achieved sufficiently.

The aforementioned biodegradable and bioabsorbable implant device forosteosynthesis is used at the site of operation for connecting fracturedbone parts, by bending and/or twisting it within the ordinarytemperature range to deform it into such a shape that it can be fittedto the fractured bone parts and then thrusting fixing screws into thebiological bone through the screw insertion hole 1. Thus, the implantmaterial of the present invention is markedly convenient, because itdoes not require a troublesome work of carrying out bending deformationby heating it at about 80° C. and its shape can be adjusted easily bybending or torsional deformation at ordinary temperature and becausethere is no fear of returning to its original shape in the living body.In addition, the implant material maintains sufficient strength in theliving body during a period of from 1 to 6 months, starting from thecommencement of hydrolysis on its surface through its contact with thebody fluid until healing of the fractured bone parts, but is finelybroken thereafter as its hydrolysis progresses and finally absorbed bythe living body and completely disappears. In consequence, it is notnecessary to take out the material from the living body by re-operationwhich is common in the case of conventional metallic implant materials,so that mental and economical burdens on patients can be alleviated.

It is desirable to include a bioceramics powder in the aforementionedplate-shaped implant material for osteosynthesis use, because thebioceramics powder which is present on the surface layer or appeared onthe surface by hydrolysis of the polymer allows calcium phosphate orbone tissue in the living body to deposit on or conduct to the surfacelayer region of the implant material, so that the implant material canbind to the living bone and fix the fractured bone parts securely withina relatively short period of time.

Examples of the bioceramics powder to be used include powders ofsurface-bioactive sintered hydroxyapatite, glass for biological body useof a bioglass or crystallized glass system, biodegradable un-sinteredhydroxyapatite (namely, a raw hydroxyapatite which is not treated bysintering or by both sintering or calcination but has a chemicalcomposition similar to that of hydroxyapatite in the living body),dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate,octacalcium phosphate, calcite and diopside, which may be used alone oras a mixed powder of two or more.

It is desirable to use the bioceramics powder at a blending ratio ofapproximately from 10 to 60% by weight, because the function ofbioceramics powder to effect deposition or conduction of calciumphosphate and bone tissue in the living body cannot fully be exertedwhen the ratio is less than 10% by weight, and the implant materialbecomes brittle due to reduced toughness when the ratio exceeds 60% byweight.

Examples of the present invention are given below by way of illustrationand not by way of limitation.

EXAMPLE 1

Using an extruder, a poly-L-lactic acid (PLLA) having a viscosityaverage molecular weight of 350,000 was melt-extruded at 190° C. toobtain a prismatic billet of 250,000 in viscosity average molecularweight having a rectangular section of 12 mm in length×50 mm in width.

This billet was forged at 110° C. by press-charging it into the cavityof a forming mold of 7.5 mm in height×32 mm in width×60 mm in length,thereby obtaining a molding. This molding was again subjected to theforging molding by changing its mechanical direction (MD) to obtain aplate-shaped multi-axially orientated compression molding of 60 mm inlength×80 mm in width×3 mm in thickness. Crystallinity of thismulti-axially orientated compression molding was calculated to be 43%when measured by a differential scanning calorimeter (DSC).

As shown in FIG. 5, this multi-axially orientated compression moldingwas cut out at a direction of 0°, 45° or 90° to prepare a rectangularplate of 30 mm in length×5 mm in width×1.5 mm in thickness. Thereafter,its bending strength was measured using an autograph. The results areshown in Table 1. In this connection, temperature at the time ofmeasurement was 22° C. (room temperature).

As shown in FIG. 6A, using each of the aforementioned plates cut out ina direction of 0°, 45° or 90°, the plate P was pressed at its centralposition with a cross head 2 of the autograph until its bending anglebecame 150°, and the load at that time was measured. Also, as shown inFIG. 6B, the thus treated plate P was turned over to measure the load atthe time when the bending angle again became 150°, and this step wasrepeated 20 times to measure retaining ratio of the bending strength.Results of the measurement of the plate cut out in the direction of 0°was shown in the graph of FIG. 7, results of the measurement of theplate cut out in the direction of 45° was shown in the graph of FIG. 8and results of the measurement of the plate cut out in the direction of90° was shown in the graph of FIG. 9.

COMPARATIVE EXAMPLE 1

For the sake of comparison, the prismatic billet obtained in Example 1was heated at 110° C. and uniaxially drawn at a draw ratio of 2.5. Thethus drawn molding was cut out in a direction of 0°, 45° or 90° usingthe uniaxially drawn direction as 0°, thereby preparing a rectangularplate of 30 mm in length×5 mm in width×1.5 mm in thickness, and eachplate was subjected to bending strength test and repeated bendingstrength test in the same manner as described in Example 1. Results ofthe bending strength test are shown in the following Table 1, andresults of the repeated bending strength test are comparatively shown inthe graph of FIG. 7 (cut out direction: 0°), the graph of FIG. 8 (cutout direction: 45°) and the graph of FIG. 9 (cut out direction: 90°).

TABLE 1 Bending strength (MPa) 0° 45° 90° Example 1 Multi-axiallyoriented 265 260 258 compression molding of PLLA {overscore (Mv)} =250,000 (average) Comparative Uniaxially drawn and 220 213 205 Example 1oriented molding of PLLA {overscore (Mv)} = 250,000 (average)

As is evident from Table 1, all of the plates cut out in the cut outdirections of 0°, 45° and 90° from the multi-axially orientedcompression molding of Example 1 showed an initial bending strength ofaround 260 MPa which was higher than the bending strength of biologicalbone (200 MPa). Also, difference in the cut out direction does not causesignificant difference in the bending strength, so that these plateshave almost the same bending strength and do not show anisotropy in viewof strength. On the other hand, the uniaxially drawn plates showed lowerstrength than the above, and anisotropy in view of strength was found.

In addition, as is evident from the graphs of FIGS. 7 to 9, bendingstrength of the plate of Example 1 cut out in any direction decreased to80% (212 MPa) of its initial bending strength by the 1st to 5th bendingdeformation caused by the residual distortion at the time of molding,but the residual distortion disappeared thereafter by the shapeadjustment so that the strength was not substantially decreased andabout 80% of the initial bending strength was maintained until 20thbending deformation, and breakage of the plate did not occur. It isevident from these results that each of the plates of Example 1 is aplate which maintains a strength higher than the bending strength ofbiological bone even against severe repeated bending deformation at roomtemperature (22° C.) and has toughness showing no anisotropy in view ofthe bending strength and its retaining ratio.

In the case of the plates of Comparative Example 1, on the contrary,anisotropy was observed in terms of bending strength and its retainingratio by the repeated bending deformation, and the plate cut out at 0°maintained the strength most long but its bending strength decreasedwhen the number of times of bending deformation exceeded 12 and reducedto about 35% of the initial bending strength by 19th bendingdeformation. On the other hand, the plate cut out in the direction of45° showed rapid reduction of the strength retaining ratio when thenumber of bending deformation exceeded 5 times and was broken by fatigueby the 10th bending deformation. Also, the plate cut out in thedirection of 90° was broken by the 2nd bending deformation. Accordingly,the plate oriented by uniaxial drawing was a plate having no toughness,which showed not only low initial bending strength but also significantanisotropy in view of the retaining ratio of strength by repeatedbending deformation.

In this connection, deformation restoration was not observed when aplate deformed at ordinary temperature (particularly a plate bent at aroom temperature of 37° C. or less) was soaked in hot water of 37° C.for 10 days or more.

EXAMPLE 2

Using granules of PLLA having a viscosity average molecular weight of250,000 in which 40% by weight of un-sintered and un-calcinedhydroxyapatite (u-HA) was uniformly dispersed, a plate-shapedmulti-axially oriented compression molding having a viscosity averagemolecular weight of 160,000 containing u-HA was obtained in the samemanner as described in Example 1. The thus obtained multi-axiallyoriented compression molding was subjected to cutting processing to cutout in a direction of 0°, 45° or 90° in the same manner as described inExample 1, thereby preparing a rectangular plate of 30 mm in length×5 mmin width×1.5 mm in thickness, and each plate was subjected to bendingstrength test and repeated bending strength test in the same manner asdescribed in Example 1.

As the results, the initial bending strength of the plate cut out in thedirection of 0° was 268 MPa, that of the plate cut out in the directionof 450 was 266 MPa and that of the plate cut out in the direction of 90°was 262 MPa, each of which showing higher bending strength than that ofbiological bone (200 MPa), and difference in the bending strength washardly found by the cut out direction. In addition, due to theadjustment and disappearance of residual distortion, bending strength ofthe plate cut out in any direction was decreased to about 80% of itsinitial bending strength by the 1st to 5th bending deformation but wasnot substantially decreased thereafter, the strength retaining ratio wasabout 75% at the time of the 20th bending deformation, and breakage ofthe plate did not occur. It is evident from these results that each ofthe plates comprises a multi-axially oriented compression moldingcontaining a bioceramics powder is also a plate which has toughness anddoes not show anisotropy in view of the bending strength and itsretaining ratio. In this connection, deformation restoration was notfound at 37° C.

EXAMPLE 3

In the same manner as described in Example 1, a prismatic billet of250,000 in viscosity average molecular weight having a rectangularsection of 10 mm in length×25 mm in width.

This billet was forged at 110° C. by press-charging it into the cavityof a forming mold of 5 mm in height×20 mm in width×300 mm in length,thereby obtaining a molding. This molding was again subjected to theforging molding by changing its mechanical direction (MD) to obtain aplate-shaped multi-axially orientated compression molding of 300 mm inlength×45 mm in width×2.5 mm in thickness. A prism of 2.5 mm inheight×2.5 mm in width×300 mm in length was prepared by cutting theplate-shaped molding, and a wire having a circular section of 1.5 mm φwas prepared by cutting corners of the prism.

As shown in FIG. 10A, one end of the thus prepared wire was fixed withtwo metal plates, and the other end was fixed by holding it between twocylinders. As shown in FIG. 10B, this wire was bent until its bendingangle became 15° against its central point, and the load at that timewas measured. Also, as shown in FIG. 10C, this wire was again bentupward to measure the load at the time when the bending angle againbecame 15°, and this step was repeated 800 times to measure retainingratio of the bending strength.

For the sake of comparison, a kirschner having a thickness of 1.5 mm φwas measured in the same manner. The results of measurement are shown inFIG. 11.

As is evident from FIG. 11, strength of the kirschner wire was decreasedto 80% of its initial bending strength by the 50th bending deformation.Thereafter, decrease in the strength was not found until 200 to 300times of bending deformation, but the strength was gradually decreasedby 300 or more times of bending deformation, and the wire was broken bythe 400th bending deformation.

On the contrary, the PLLA wire retained its initial bending strength bythe 800th bending deformation and was not broken. Accordingly, it isevident that the PLLA wire is a wire having stronger toughness than thekirschner wire, which can retain its strength even against severerepeated bending deformation at room temperature (22° C.).

EXAMPLE 4

A wire having a diameter of 1 mm prepared as described above was bentuntil the bending angle became 90° downward or upward. One hundred X Rayphotographs at the bent part were taken to analyze the change ofmicrocrystalline orientation with extremely high accuracy.

With respect to the wire bent upward at 90°, about 65% of themicrocrystals were slanted at 72.50, but about 20% of the microcrystalsdid not follow the orientation. The orientation was distributed fromabout 65° to about 80° and predominantly within the range of about11.50. With respect to the wire bent downward at 90°, the similartendency in the orientation was found in the direction of the bending,but the orientation was distributed in a wider range of about 22.5°.About 15% of the microcrystals were oriented in the direction of 30upward.

The result shown above means that bending the wire at ordinarytemperature causes the orientation direction change of the crystalchains oriented along many axes or clusters thereof, and the changeoccurs with a distribution. In other words, it was found that themicrocrystalline distribution changes from a place to a place based onthe stress relaxation accompanying the deformation by the outer force atordinary temperature. Thus, it is considered that the orientation ofmicrocrystals that followed the deformation supports the strength alongwith the direction of deformation and the orientation of crystals thatremained intact supports the original strength before deformation.

EXAMPLE 5

Using the billet obtained in Example 1, a molding (plate) forged onetime in the direction of MD1 and a molding (plate) further forged in thedirection of TD direction (i.e., MD2) were prepared. The state ofcrystal orientation of these moldings were analyzed by the X raydiffraction method (analysis by the X ray transmission photography usinga wide X ray flat camera). Several samples were layered to measure awide range of intensity and about ten X ray photographs were taken foreach of the place in order to achieve accurate analysis. The deformationratio of the first and second forgings was 2.5, respectively. MD1 andMD2 forms an angle of 90°, i.e., in the relation of MD and TD.Representative photographs are shown as FIGS. 12A, 12B, 13A, and 13B.

FIG. 12A is an X ray photograph of the molding forged one time, when theincident angle of the X ray was parallel to the mechanical directionMD1. In this photograph, the diffraction of axis a and axis b draws acircle but the intensity is not symmetric about the meridian (confirmedby the measurement using a slanted sample), which indicates that theorientation of paracrystals was slanted at an angle of 10° toward theoperation axis. In this regard, the angle of the tapered part of theforming mold for the forging was 15°.

FIG. 12B is an X ray photograph of the molding forged one time, when theincident angle of the X ray was right to the mechanical direction MD1.The photograph shows developed layered lines and remarkable spotsappeared asymmetrically about the equator. The results support that themolecular chains were slanted toward the operation axis.

FIG. 13A is an X ray photograph of the molding forged two timesaccording to the present invention, when the incident angle of the X raywas parallel to the mechanical direction MD2 (i.e., right to the platesurface). FIG. 13B is an X ray photograph of the molding forged twotimes according to the present invention, when the incident angle of theX ray was right to the mechanical direction MD2 (i.e., parallel to theplate surface). As is understood from these results, a part layered inthe thickness direction was found at the center part of the plate. Thesephotographs in combination indicate that molecular chains were orientedwith many reference axes and state of crystals was considerablyirregular.

From the above results, it was confirmed that the crystals oriented witha slant of about 10° toward MD after the first forging changed to havean assembled morphology having many reference axes by the secondforging. FIG. 14 shows the process of the formation and morphologicalchange of the orientation. As a result, it was suggested that thismorphology is the scientific reason why the material of the presentinvention shows strength in the various directions against deformation.

Thus, as has been described in the foregoing, the biodegradable andbioabsorbable implant device of the present invention exerts manyremarkable effects, for example, because it has high mechanical strengthand its shape after deformation such as bending and twisting withinordinary temperature range can be fixed and maintained, its shape can beeasily adjusted at the site of operation, since it has substantially noanisotropy in view of strength, it does not cause whitening, breakageand sharp decrease in strength (deterioration) when its bendingdeformation is repeated in any direction and it has toughness, and theimplant material for osteosynthesis use which contains a bioceramicspowder can bind to bones and fix the fractured bone parts withoutloosening within a short period of time.

In addition, the shape-adjusting method of the present invention is amethod by which shapes of the implant material can be easily adjusteddue to the employment of a means that overturns common knowledge on thedeformation of plastics, namely a means to carry out bending deformationand torsional deformation within ordinary temperature range, so that thetroublesome prior art deformation by heating at a high temperature canbe avoided.

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof.

This application is based on Japanese patent application No.Hei.-10-279389 filed on Sep. 14, 1998, incorporated herein by reference.

What is claimed is:
 1. A biodegradable and bioabsorbable implantmaterial which comprises a biodegradable and bioabsorbable crystallinepolymer capable of effecting deformation within ordinary temperaturerange and having a shape-keeping ability to fix and maintain the shapeafter deformation as such, wherein molecular chains, domains ofmolecular chain assembly or crystals of the biodegradable andbioabsorbable polymer are multi-axially oriented alongthree-dimensionally oriented reference axes having different axialdirections, or clusters having these reference axes having differentorientation are assembled.
 2. The biodegradable and bioabsorbableimplant material according to claim 1, wherein it is obtained by forginga billet comprising a biodegradable and bioabsorbable crystallinepolymer at a low temperature and then forging the same at a lowtemperature by changing its mechanical direction.
 3. The biodegradableand bioabsorbable implant material according to claim 1, wherein thebiodegradable and bioabsorbable crystalline polymer is a crystallinepolylactic acid.
 4. The biodegradable and bioabsorbable implant materialaccording to claim 1, wherein it is formed into a flat heteromorphicshape.
 5. The biodegradable and bioabsorbable implant material accordingto claim 1, wherein it is formed into a cylindrical shape.
 6. Thebiodegradable and bioabsorbable implant material according to claim 1,wherein it further comprises a bioceramics powder.
 7. The biodegradableand bioabsorbable implant material according to claim 1, wherein thestate of orientation of molecular chains, domains of molecular chainassembly or crystals of the biodegradable and bioabsorbable polymerpartially changes by the deformation within ordinary temperature.
 8. Amethod for adjusting shape of a biodegradable and bioabsorbable implantmaterial, which comprises effecting bending deformation and/or torsionaldeformation of the biodegradable and bioabsorbable implant material asset forth in any one of claims 1 to 7 within ordinary temperature range.9. The biodegradable and bioabsorbable implant material according toclaim 4, wherein the flat heteromorphic shape is a sheet, a plate, aplate having screw-inserting hole(s), a washer, a button, a mesh or aribbon.
 10. The biodegradable and bioabsorbable implant materialaccording to claim 5, wherein the cylindrical shape is a wire, a cable,a rod or a pin.